CA2325776C - Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent - Google Patents
Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent Download PDFInfo
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- CA2325776C CA2325776C CA002325776A CA2325776A CA2325776C CA 2325776 C CA2325776 C CA 2325776C CA 002325776 A CA002325776 A CA 002325776A CA 2325776 A CA2325776 A CA 2325776A CA 2325776 C CA2325776 C CA 2325776C
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- alkyl
- pharmaceutically acceptable
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 119
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 title description 4
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title description 4
- 229940127093 camptothecin Drugs 0.000 title description 4
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 title description 4
- 239000002253 acid Substances 0.000 claims abstract description 33
- -1 perhaloalkyl Chemical group 0.000 claims abstract description 31
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
- 125000003118 aryl group Chemical group 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 125000000466 oxiranyl group Chemical group 0.000 claims abstract description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 4
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 45
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- CEXHYAFUVODQOF-UHFFFAOYSA-N chembl327547 Chemical compound FC1=C(F)C=C2C=C(CN3C4=CC5=C(C3=O)CC(=O)C5(O)CC)C4=NC2=C1 CEXHYAFUVODQOF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 150000002940 palladium Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- 239000000047 product Substances 0.000 description 82
- 239000000243 solution Substances 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000007858 starting material Substances 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000003480 eluent Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 17
- 238000004587 chromatography analysis Methods 0.000 description 16
- 239000002609 medium Substances 0.000 description 14
- 239000012429 reaction media Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000001819 mass spectrum Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- KGDFHGMTFPQPSG-UHFFFAOYSA-N 2-bromo-3-(bromomethyl)quinoline Chemical compound C1=CC=C2N=C(Br)C(CBr)=CC2=C1 KGDFHGMTFPQPSG-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 150000002596 lactones Chemical group 0.000 description 3
- RDPLOLUNEKBWBR-UHFFFAOYSA-L magnesium;sodium;sulfate Chemical compound [Na+].[Mg+2].[O-]S([O-])(=O)=O RDPLOLUNEKBWBR-UHFFFAOYSA-L 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
- IFXZQSXMHWZLKA-UHFFFAOYSA-N 2-bromo-3-(bromomethyl)-6,7-difluoroquinoline Chemical compound BrCC1=C(Br)N=C2C=C(F)C(F)=CC2=C1 IFXZQSXMHWZLKA-UHFFFAOYSA-N 0.000 description 2
- VONGIOGTLFSXDE-UHFFFAOYSA-N 2-fluoro-4-iodopyridine-3-carbaldehyde Chemical compound FC1=NC=CC(I)=C1C=O VONGIOGTLFSXDE-UHFFFAOYSA-N 0.000 description 2
- XRTISYRXTFJCCB-UHFFFAOYSA-N 3-(1,3-dioxolan-2-yl)-2-fluoro-4-iodopyridine Chemical compound FC1=NC=CC(I)=C1C1OCCO1 XRTISYRXTFJCCB-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- RTVFPALRFSMTTJ-UHFFFAOYSA-N 5-ethyl-10,20-diazapentacyclo[10.8.0.02,10.04,8.014,19]icosa-1,3,6,8,11,13,15,17,19-nonaen-5-ol Chemical compound C(C)C1(C=CC2=CN3C=C4C(N=C5C=CC=CC5=C4)=C3C=C21)O RTVFPALRFSMTTJ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229940072033 potash Drugs 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- FQCZQIGAGKWNEA-UHFFFAOYSA-N (2-fluoro-4-iodopyridin-3-yl)methanol Chemical compound OCC1=C(F)N=CC=C1I FQCZQIGAGKWNEA-UHFFFAOYSA-N 0.000 description 1
- BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 1
- AHYUZVLARFPNKD-UHFFFAOYSA-N 10,20-diazapentacyclo[10.8.0.02,10.04,8.014,19]icosa-1,3,5,7,11,13,15,17,19-nonaen-9-one Chemical compound C=1C2=CC=3C(N=C2C=CC=1)=C1C=C2C(C(N1C=3)=O)=CC=C2 AHYUZVLARFPNKD-UHFFFAOYSA-N 0.000 description 1
- JJQSAKWZRMBCEJ-UHFFFAOYSA-N 19-ethyl-19-hydroxy-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,17-dione Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)CC(=O)CC5(O)CC)C4=NC2=C1 JJQSAKWZRMBCEJ-UHFFFAOYSA-N 0.000 description 1
- PKQMKOXOWOJEJD-UHFFFAOYSA-N 19-ethyl-19-hydroxy-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)CCC(=O)C5(O)CC)C4=NC2=C1 PKQMKOXOWOJEJD-UHFFFAOYSA-N 0.000 description 1
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
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- 244000309464 bull Species 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
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- 239000003054 catalyst Substances 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
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- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000003997 cyclic ketones Chemical group 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- LJOQGZACKSYWCH-UHFFFAOYSA-N dihydro quinine Natural products C1=C(OC)C=C2C(C(O)C3CC4CCN3CC4CC)=CC=NC2=C1 LJOQGZACKSYWCH-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- JMVOCSLPMGHXPG-UHFFFAOYSA-N dipotassium;dioxido(dioxo)osmium Chemical compound [K+].[K+].[O-][Os]([O-])(=O)=O JMVOCSLPMGHXPG-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- CEALXSHFPPCRNM-UHFFFAOYSA-L disodium;carboxylato carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OC([O-])=O CEALXSHFPPCRNM-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- YAGKRVSRTSUGEY-UHFFFAOYSA-N ferricyanide Chemical compound [Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] YAGKRVSRTSUGEY-UHFFFAOYSA-N 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- YHPHNGGWPOGUPY-UHFFFAOYSA-N methyl 2-(2-fluoro-3-methylpyridin-4-yl)-2-hydroxybutanoate Chemical compound COC(=O)C(O)(CC)C1=CC=NC(F)=C1C YHPHNGGWPOGUPY-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- XPIWVCAMONZQCP-UHFFFAOYSA-N methyl 2-oxobutanoate Chemical compound CCC(=O)C(=O)OC XPIWVCAMONZQCP-UHFFFAOYSA-N 0.000 description 1
- GRKQYIMIQMHOQD-UHFFFAOYSA-N methyl 3-(2-fluoro-3-formylpyridin-4-yl)-3-hydroxypentanoate Chemical compound COC(=O)CC(O)(CC)C1=CC=NC(F)=C1C=O GRKQYIMIQMHOQD-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical compound OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- DFNPRTKVCGZMMC-UHFFFAOYSA-M tributyl(fluoro)stannane Chemical compound CCCC[Sn](F)(CCCC)CCCC DFNPRTKVCGZMMC-UHFFFAOYSA-M 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR99.14499 | 1999-11-18 | ||
| FR9914499A FR2801309B1 (fr) | 1999-11-18 | 1999-11-18 | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2325776A1 CA2325776A1 (fr) | 2001-05-18 |
| CA2325776C true CA2325776C (fr) | 2007-02-20 |
Family
ID=9552253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002325776A Expired - Fee Related CA2325776C (fr) | 1999-11-18 | 2000-11-17 | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6509345B2 (zh) |
| EP (1) | EP1101765B1 (zh) |
| JP (1) | JP3545332B2 (zh) |
| KR (1) | KR100460785B1 (zh) |
| CN (2) | CN1158282C (zh) |
| AT (1) | ATE222253T1 (zh) |
| AU (1) | AU772609B2 (zh) |
| BR (1) | BR0005486A (zh) |
| CA (1) | CA2325776C (zh) |
| DE (1) | DE60000328T2 (zh) |
| DK (1) | DK1101765T3 (zh) |
| EA (1) | EA003206B1 (zh) |
| ES (1) | ES2180501T3 (zh) |
| FR (1) | FR2801309B1 (zh) |
| HK (2) | HK1036803A1 (zh) |
| HU (1) | HUP0004573A3 (zh) |
| MX (1) | MXPA00011238A (zh) |
| NO (1) | NO318464B1 (zh) |
| NZ (1) | NZ508248A (zh) |
| PL (1) | PL202231B1 (zh) |
| PT (1) | PT1101765E (zh) |
| SI (1) | SI1101765T1 (zh) |
| ZA (1) | ZA200006730B (zh) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2256552T3 (es) * | 2001-10-05 | 2006-07-16 | F. Hoffmann-La Roche Ag | Compuestos policiclicos que tienen actividad anti-tumoral. |
| US7071204B2 (en) * | 2003-06-30 | 2006-07-04 | Research Triangle Institute | Camptothecin analogs having an E-ring ketone |
| FR2889528B1 (fr) * | 2005-08-05 | 2007-09-07 | Servier Lab | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2889527A1 (fr) * | 2005-08-05 | 2007-02-09 | Servier Lab | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2892417B1 (fr) * | 2005-10-24 | 2010-10-22 | Servier Lab | Nouveaux composes aminoesterifies a cycle e hydrocarbone a sept chainons analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2892418B1 (fr) * | 2005-10-24 | 2010-10-22 | Servier Lab | Nouveaux composes aminoesterifies a cycle e hydrocarbone a six chainons analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2658015A1 (en) | 2006-03-30 | 2007-10-11 | Diatos S.A. | Camptothecin-peptide conjugates and pharmaceutical compositions containing the same |
| CN103288842B (zh) * | 2012-02-24 | 2016-01-13 | 中国人民解放军第二军医大学 | 氟取代e环喜树碱类似物及其作为药物的用途 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5829793B2 (ja) * | 1975-02-07 | 1983-06-24 | 日本ケミフア （株） | ７−アルコキシカルボニル−８−メチルインドリジノ〔１，２−ｂ〕キノリン−９（１１Ｈ）−オンの製法 |
| JPS58435B2 (ja) * | 1975-12-23 | 1983-01-06 | カメタニ テツジ | ルテカルピンノセイホウ |
| GB8513460D0 (en) * | 1985-05-29 | 1985-07-03 | Glaxo Group Ltd | Chemical compounds |
| US4939255A (en) * | 1987-06-24 | 1990-07-03 | Daiichi Pharmaceutical Co., Ltd. | Hexa-cyclic camptothecin derivatives |
| US5004758A (en) * | 1987-12-01 | 1991-04-02 | Smithkline Beecham Corporation | Water soluble camptothecin analogs useful for inhibiting the growth of animal tumor cells |
| CA2102123A1 (en) * | 1991-07-22 | 1993-01-23 | Edwin M. Marker, Jr. | Reagent handling system for automated clinical analyzer apparatus |
| US5391745A (en) * | 1992-07-23 | 1995-02-21 | Sloan-Kettering Institute For Cancer Research | Methods of preparation of camptothecin analogs |
| PT835258E (pt) * | 1995-06-21 | 2003-02-28 | Sod Conseils Rech Applic | Novos analogos de camptotecina, processos para a sua preparacao, sua utilizacao como farmacos e composicoes farmaceuticas que os contem |
| UA57757C2 (uk) * | 1996-12-20 | 2003-07-15 | Сос'Єте Де Консей Де Решерш Е Даплікасьон С'Єнтіфік (С.К.Р.А.С.) | Аналоги камптотецину, спосіб їх отримання (варіанти) і фармацевтична композиція |
| DE19815812A1 (de) * | 1998-04-08 | 1999-10-14 | Bayer Ag | Modifizierte Cytostatika |
| US6043367A (en) * | 1998-09-30 | 2000-03-28 | Roffler; Steve | Proactive antitumor compounds |
-
1999
- 1999-11-18 FR FR9914499A patent/FR2801309B1/fr not_active Expired - Fee Related
-
2000
- 2000-11-09 DE DE60000328T patent/DE60000328T2/de not_active Expired - Lifetime
- 2000-11-09 SI SI200030016T patent/SI1101765T1/xx unknown
- 2000-11-09 EP EP00403108A patent/EP1101765B1/fr not_active Expired - Lifetime
- 2000-11-09 DK DK00403108T patent/DK1101765T3/da active
- 2000-11-09 ES ES00403108T patent/ES2180501T3/es not_active Expired - Lifetime
- 2000-11-09 PT PT00403108T patent/PT1101765E/pt unknown
- 2000-11-09 AT AT00403108T patent/ATE222253T1/de active
- 2000-11-15 MX MXPA00011238A patent/MXPA00011238A/es unknown
- 2000-11-16 JP JP2000348947A patent/JP3545332B2/ja not_active Expired - Fee Related
- 2000-11-17 AU AU71683/00A patent/AU772609B2/en not_active Ceased
- 2000-11-17 NO NO20005807A patent/NO318464B1/no not_active IP Right Cessation
- 2000-11-17 CN CNB001284606A patent/CN1158282C/zh not_active Expired - Fee Related
- 2000-11-17 NZ NZ508248A patent/NZ508248A/en not_active IP Right Cessation
- 2000-11-17 KR KR10-2000-0068441A patent/KR100460785B1/ko not_active IP Right Cessation
- 2000-11-17 CA CA002325776A patent/CA2325776C/fr not_active Expired - Fee Related
- 2000-11-17 ZA ZA200006730A patent/ZA200006730B/xx unknown
- 2000-11-17 EA EA200001084A patent/EA003206B1/ru not_active IP Right Cessation
- 2000-11-17 PL PL343949A patent/PL202231B1/pl not_active IP Right Cessation
- 2000-11-17 HU HU0004573A patent/HUP0004573A3/hu unknown
- 2000-11-17 CN CNB200410045949XA patent/CN1304395C/zh not_active Expired - Fee Related
- 2000-11-21 BR BR0005486-0A patent/BR0005486A/pt not_active IP Right Cessation
-
2001
- 2001-11-05 US US10/010,380 patent/US6509345B2/en not_active Expired - Fee Related
- 2001-11-07 HK HK01107780A patent/HK1036803A1/xx not_active IP Right Cessation
-
2005
- 2005-06-06 HK HK05104726A patent/HK1071892A1/xx not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20131119 |